This is a single arm, phase II trial of combined neoadjuvant platinum doublet chemotherapy plus durvalumab followed by surgery, postoperative radiation and adjuvant durvalumab for 13 cycles for patients with potentially resectable stage IIIA and IIIB (T1-3, N2) NSCLC (per the 8th International Association for the Study of Lung Cancer classification). The primary objective of this study is to increase N2 nodal clearance (N2NC) to 50% or greater for combined platinum doublet chemotherapy with durvalumab induction therapy from historical rate of 30% for platinum doublet chemotherapy alone in patients with potentially resectable stage IIIA/B (N2) NSCLC.
In the preoperative period, patients who have undergone adequate mediastinal evaluation and are considered operable will be treated with durvalumab 1125 mg IV every 3 weeks (Q3W) in combination with platinum doublet chemotherapy (cisplatin with pemetrexed or docetaxel, depending upon histology). Patients will undergo postoperative radiation (54Gy) within 4-10 weeks after surgery (unless single station N2 at registration with resultant ypT0N0 after neoadjuvant therapy). One to 6 weeks after completion of radiation, patients will receive adjuvant durvalumab 1500 mg IV every 4weeks (Q4W) for 1 year. Patients who do not have surgery due to refusal, physician decision, or local and distant progression will have to discontinue study treatment. All participants will have imaging assessment prior to surgery after Cycle 2 (Week 6) and after Cycle 4 (Weeks 13 15). Patients will undergo potentially curable surgery as per standard of care. Patients will undergo imaging assessment every 12 weeks after surgery for 2 years, then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Preoperative Treatment: * Non-squamous NSCLC: durvalumab 1125 mg, followed by pemetrexed 500 mg/m2 IV with cisplatin 75 mg/m2 IV, every 3 weeks, for 4 cycles * Squamous NSCLC: durvalumab 1125 mg, followed by docetaxel 75 mg/m2 IV with cisplatin 75 mg/m2 IV, every 3 weeks, for 4 cycles Adjuvant Therapy: • 1-6 weeks after completion of radiotherapy, durvalumab 1500 mg IV every 4 weeks will be administered for 13 cycles.
Patients will be re-evaluated following preoperative treatment to assess if patient is still medically fit to withstand surgery. Eligible patients will then undergo lobectomy, bilobectomy, sleeve lobectomy or other extended resection, or a pneumonectomy will be performed at the discretion of the attending thoracic surgeon.
4-10 weeks after surgery, patients will receive 54 Gy of radiotherapy with single daily fractions.
NorthWestern University
Chicago, Illinois, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Lowell General Hospital
Lowell, Massachusetts, United States
SUNY Upstate Medical University
Syracuse, New York, United States
Baptist Cancer Center
Memphis, Tennessee, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
University of Virginia Health System
Charlottesville, Virginia, United States
N2 nodal clearance (N2NC)
To increase N2 nodal clearance (N2NC) to 50% or greater for combined platinum doublet chemotherapy with durvalumab induction from an historical rate of 30% for platinum doublet chemotherapy alone in patients with potentially resectable stage IIIA/B (N2) NSCLC.
Time frame: 5 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
To evaluate the safety and tolerability of neoadjuvant platinum doublet chemotherapy and durvalumab followed by surgery followed by adjuvant radiation and durvalumab.
Time frame: 5 years
Radiographic response rate
To assess the radiographic response rate of neoadjuvant platinum doublet chemotherapy and durvalumab.
Time frame: 5 years
Rate of major pathologic response and pathologic complete response
To evaluate the rate of major pathologic response and pathologic complete response in the resected primary tumor and lymph nodes following neoadjuvant combination therapy.
Time frame: 16 weeks
Evaluate event free survival (EFS)
EFS evaluated from the time of registration to one of the following events, whichever comes first: a) radiographic disease progression, b) local progression as defined by lymph node progression precluding surgery, c) inability to resect the tumor, d) local or distant recurrence, e) death due to any cause.
Time frame: 5 years
Overall survival rate
To evaluate overall survival rate from the time of registration
Time frame: 5 years
Rate of complete resection.
To assess the rate of complete resection.
Time frame: 16 weeks
Post-operative complications
To assess post-operative complications
Time frame: Within 30 days of surgery
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